Title | RS1, a discoidin domain-containing retinal cell adhesion protein associated with X-linked retinoschisis, exists as a novel disulfide-linked octamer |
Publication Type | Journal Article |
Year of Publication | 2005 |
Authors | Wu, WWH, Wong, JP, Kast, J, Molday, RS |
Journal | Journal of Biological Chemistry |
Volume | 280 |
Pagination | 10721-10730 |
Date Published | Mar |
Type of Article | Article |
ISBN Number | 0021-9258 |
Keywords | C2 DOMAIN, COAGULATION-FACTOR-V, CRYSTAL-STRUCTURES, EXPRESSION, FACTOR-VIII, GENE, JUVENILE RETINOSCHISIS, MUTATIONS, PHOTORECEPTOR, RESOLUTION |
Abstract | RS1, also known as retinoschisin, is an extracellular protein that plays a crucial role in the cellular organization of the retina. Mutations in RS1 are responsible for X-linked retinoschisis, a common, early-onset macular degeneration in males that results in a splitting of the inner layers of the retina and severe loss in vision. RS1 is assembled and secreted from photoreceptors and bipolar cells as a homo-oligomeric protein complex. Each subunit consists of a 157-amino acid discoidin domain flanked by two small segments of 39 and 5 amino acids. To begin to understand how the structure of RS1 relates to its role in retinal cell adhesion and X-linked retinoschisis, we have determined the subunit organization and disulfide bonding pattern of RS1 by SDS gel electrophoresis, velocity sedimentation, and mass spectrometry. Our results indicate that RS1 exists as a novel octamer in which the eight subunits are joined together by Cys(59)-Cys(223) intermolecular disulfide bonds. Subunits within the octamer are further organized into dimers mediated by Cys(40)-Cys(40) bonds. These cysteines lie just outside the discoidin domain indicating that these flanking segments primarily function in the octamerization of RS1. Within the discoidin domain, two cysteine pairs (Cys(63)-Cys(219) and Cys(110)-Cys(142)) form intramolecular disulfide bonds that are important in protein folding, and one cysteine (Cys(83)) exists in its reduced state. Because mutations that disrupt subunit assembly cause X-linked retinoschisis, the assembly of RS1 into a disulfide-linked homo-octamer appears to be critical for its function as a retinal cell adhesion protein. |
URL | <Go to ISI>://000227559600118 |
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